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Biomedical subjects

C Bourgain

Publications and source records attributed to C Bourgain.

At least 19 recordsLinked to original sources
PubMed2002

Missing data in haplotype analysis: a study on the MILC method.

Given the enormous progress in the knowledge of the human genome, genetic markers are now available throughout the genome. Haplotype analysis, allowing the simultaneous use of information from several markers, has thus become increasingly popular. However, we often face the problem of missing data and of haplotype identification. We have proposed a haplotype based method for the genetic study of multifactorial diseases in founder populations, the MILC method (Bourgain et al. 2000). MILC is based on the contrast of identity length between haplotypes transmitted to affected offspring and haplotype non-transmitted. In this study, the impact of different strategies, regarding missing data, on the MLIC method are evaluated. A real situation is considered where data are derived from a genome screen for asthma susceptibility alleles in the Hutterites. Results are illustrated on this asthma data set.

Asthma↗
PubMed2002

CD80 (B7-1) and CD86 (B7-2) genes and genetic susceptibility to coeliac disease.

The role of the costimulatory molecules B7-1 (CD80) and B7-2 (CD86) in T-cell activation makes them good candidates for coeliac disease susceptibility genes. We conducted a genetic linkage study of the CD80/86 gene region in the general Finnish population and in a local subisolate. No linkage was found in either population.

Antigens, CD↗
PubMed2001

Loss of nuclear BRCA1 localization in breast carcinoma is age dependent.

Abstract. Patients carrying a germ line mutation in the BRCA1 gene are predisposed to breast cancer. Somatic BRCA1 mutations were almost never reported in sporadic breast tumors, but several authors have described a decrease in BRCA1 mRNA and protein. In order to further investigate the possible role of BRCA1 in sporadic breast cancer, an improved immunohistochemical protocol was developed and applied on tissue sections obtained from 102 cancer patients belonging to two nonoverlapping age groups (less than 40 and more than 60 years). Based on the obtained BRCA1 specific nuclear staining we could distinguish two categories of breast cancer. The staining was present in almost all the nuclei of the normal and the cancer cells in about 50% of young (less than 40 years old) as well as older patients (more than 60 years old). Thus, BRCA1 does not seem to be involved in the genesis of these cancers. In the second category of patients, either a fraction of, or all tumor cells showed no nuclear staining. In this category, no nuclear BRCA1 staining could be observed in the tumor cells of 14 (27%) young and 3 (6%) older patients. Among six young patients bearing a breast tumor showing no BRCA1 nuclear staining at all, one was found to carry a BRCA1 germline mutation. Taken together, our results suggest that the molecular pathway in which the BRCA1 protein participates is disturbed in about 50% of sporadic breast cancer, this effect being more pronounced in tumors of young patients.

Adenocarcinoma↗
PubMed2001

Transduction of ovarian cancer cells: a recombinant adeno-associated viral vector compared to an adenoviral vector.

Recombinant adeno-associated virus (rAAV) vectors have emerged as vehicles for gene therapy. In addition, anti-neoplastic properties have been attributed to wild-type AAV. To take advantage of both features and to overcome technical problems associated with rAAV preparation, we developed a production method in which rAAV particles are amplified in an infectious cycle in the presence of wtAAV. This results in a 10(3)-10(4)-fold amplification of rAAV input particles. rAAV-GFP particles generated by this method were used to transduce ovarian cancer cell lines to evaluate their potential in ovarian cancer gene therapy, in comparison to a rAd-GFP vector. The transduction efficiency of NIH-OVCAR3, MDAH 2774 and SKOV3 cells with rAAV-GFP particles was low (< 1%) and did not improve by increasing the number of particles/cell. Repeated administration and continued exposure of NIH-OVCAR3 and MDAH 2774 improved transduction to over 3%. In contrast, these cell lines were more efficiently transduced by rAAV-GFP in the presence of adenovirus (approximately 15%) and by rAd-GFP (> 50%). These results indicate that in contrast to rAd vectors, rAAV particles are not suitable for therapeutic gene transfer in ovarian cancer cells unless efficient help can be provided to mediate ss to ds DNA conversion.

Adenoviridae↗
PubMed2001

Maximum identity length contrast: a powerful method for susceptibility gene detection in isolated populations.

We report the results of our analysis of the Genetic Analysis Workshop 12 simulated data set. Focusing on the isolated populations, we compare the efficiency of a new method, the maximum identity length contrast statistic (MILC) with the maximum likelihood score (MLS) in a genome screen strategy. MILC is a method based on the contrast of haplotype identity between transmitted and nontransmitted haplotypes in trios. It uses information on linkage and association. We found that MILC allows the detection of a risk factor corresponding to candidate gene 1 where the MLS fails, though the same population replicates were used. Interestingly, the association between this risk factor and the disease could not have been detected with the TDT at a genome-wide level.

Chromosome Mapping↗
PubMed2001

Ovulation induction disrupts luteal phase function.

Abnormalities in the luteal phase have been detected in virtually all the stimulation protocols used in in vitro fertilization, on both the hormonal and endometrial levels. Supraphysiological follicular or luteal sex steroid serum concentrations, altered estradiol: progesterone (E2/P) ratio, and disturbed luteinizing hormone pituitary secretion leading to corpus luteum insufficiency or a direct drug effect have been postulated as the main etiologic factors. Luteinizing hormone supports corpus luteum function, and low LH levels have been described after human menopausal gonadotropin treatment, after gonadotropin-releasing hormone (GnRH)-agonist treatment, or after GnRH-antagonist treatment. These low luteal LH levels may lead to an insufficient corpus luteum function and consequently to a shortened luteal phase or to the low luteal progesterone concentrations frequently described after ovulation induction. A direct effect of the GnRH agonist or GnRH antagonist on human corpus luteum or on human endometrium and thus on endometrial receptivity cannot be excluded, as GnRH receptors have been described in both compartments. Endometrial histology has revealed a wide range of abnormalities during the various stimulation protocols. In GnRH-agonist cycles, mid-luteal biopsies have revealed increased glandulo-stromal dyssynchrony and delay in endometrial development, strong positivity of endometrial glands for progesterone receptors, decreased alphavbeta3-integrin subunit expression, and earlier appearance of surface epithelium pinopodes. These factors suggest a shift forwards of the implantation window. Progesterone supplementation improves endometrial histology, and its necessity has been well established, at least in cycles using GnRH agonists.

Endometrium↗
PubMed2000

Use of closely related affected individuals for the genetic study of complex diseases in founder populations.

We propose a method, the maximum identity length contrast (MILC) statistic, to locate genetic risk factors for complex diseases in founder populations. The MILC approach compares the identity length of parental haplotypes that are transmitted to affected offspring with the identity length of those that are not transmitted to affected offspring. Initially, the statistical properties of the method were assessed using randomly selected affected individuals with unknown relationship. Because both nuclear families with multiple affected sibs and large pedigrees are often available in founder populations, we performed simulations to investigate the properties of the MILC statistic in the presence of closely related affected individuals. The simulation showed that the use of closely related affected individuals greatly enhances the power of the statistic. For a given sample size and type I error, the use of affected sib pairs, instead of affected individuals randomly selected from the population, could increase the power by a factor of two. This increase was related to an increase of kinship-coefficient contrast between haplotype groups when closely related individuals were considered. The MILC approach allows the simultaneous use of affected individuals from a founder population and affected individuals with any kind of relationship, close or remote. We used the MILC approach to analyze the role of HLA in celiac disease and showed that the effect of HLA may be detected with the MILC approach by typing only 11 affected individuals, who were part of a single large Finnish pedigree.

Celiac Disease↗
PubMed2000

Difficulties in the management of an incomplete form of refractory thrombotic thrombocytopenic purpura, the usefulness of vincristine.

BACKGROUND: Although several etiologies can be identified in thrombotic thrombocytopenic purpura (TTP), idiopathic cases are still frequent. Incomplete forms are more rare. Currently, the diagnosis may be made in cases of thrombocytopenia and microangiopathic hemolytic anemia. According to the literature, mortality and morbidity are significantly improved with plasma exchange. However, treatment in refractory forms remains problematic. CASE REPORT: A 33-year old woman presented with an incomplete form of TTP, refractory to a combination of therapeutics. The patient underwent plasma infusion, plasma exchange, and then was started on corticosteroids. She also received intravenous immunoglobulins and antiplatelet agents in close proximity to vincristine (Oncovin) infusion. The main biological indicators used were the platelet count, hematocrit, LDH, and the presence of schistocytes. Following vincristine treatment, the patient's condition rapidly improved. CONCLUSION: Vincristine administered after the failure of standard therapeutics was effective in this refractory form of TTP.

Adrenal Cortex Hormones↗
PubMed2000

Search for multifactorial disease susceptibility genes in founder populations.

The current challenge in biomedical research is to detect genetic risk factors involved in common complex diseases. The power to detect their role is generally poor in populations that have been large for a long time. It has been suggested that the power may be increased by taking advantage of the specificity of founder populations: linkage disequilibrium spanning larger regions and kinship coefficients being stronger than in large populations. A new method is proposed here, the Maximum Identity Length Contrast (MILC) which, in contrast with other existing methods, does not make the assumption of unique ancestry for the genetic risk factors. It is thus appropriate for a search for common genetic risk factors for complex diseases. Statistical properties of the method are discussed in realistic contexts.

Founder Effect↗
PubMed1999

Alteration of jun proto-oncogene status by plasmid transfection affects growth of human ovarian cancer cells.

The AP-1 transcription factor (the Jun and Fos proteins) is suspected of playing an important role in the biology of human cancer. Human epithelial ovarian tumors and cancer cell lines express the c-jun and jun-B proto-oncogenes at a high level, in contrast with the jun-D gene. We have investigated here the functional relevance of these observations for the growth of ovarian cancer cells. Transient constitutive expression of a dominant negative c-jun mutant (TAM67) in human AZ224, SKOV3 and OVCAR3 ovarian cancer cells inhibited the outgrowth of selection marker-resistant colonies by at least 75% as opposed to a control plasmid. Transfection of jun-B did not affect these cell lines, while jun-D transfection had a cell line-specific effect. In comparison, transfection of the tumor-suppressor gene p53 had a less important inhibitory effect on OVCAR3 cells and no effect on SKOV3 and AZ224 cells when compared to TAM67. Regulated TAM67 expression in AZ224 cells, from plasmids containing the mouse metallothionein or the MMTV promoter, suppressed cancer cell growth in vitro and in nude mice without evidence of increased cell death. Our observations support a role for the c-jun proto-oncogene as a positive mediator of human ovarian cancer cell growth and make it a potential therapeutic target.

Animals↗
PubMed1999

Light and electron microscopic analysis of human testicular spermatozoa and spermatids from frozen and thawed testicular biopsies.

The morphological changes caused by freezing and thawing human testicular spermatozoa have been assessed here. Retrieval of testicular biopsies was carried out on six patients with obstructive azoospermia preparatory to intracytoplasmic sperm injection (ICSI). Light microscope analysis was carried out on testicular cells and ultrastructural analysis was carried out on spermatozoa and different spermatid stages before and after the freezing procedure. Upon examination under light microscopy, all germ cells presented increased vacuolization in their cytoplasm and shrinkage or swelling of the nuclei and cytoplasmic membranes. These altered structures were accentuated in the spermatocyte I cell which often presented disrupted membranes. The ultrastructural findings under transmission electron microscopy demonstrated that after freezing and thawing the major types of cryoinjury were the swelling and rupture of inner and outer acrosomal and plasma membranes. The acrosome material often appeared as dispersed material or as condensed spots or was even lost. Such damage was observed mainly at the spermatozoa and late spermatid stages. We conclude that the freezing and thawing of testicular biopsies causes similar morphological damage to testicular spermatozoa and frozen-thawed ejaculated spermatozoa. It is still unclear whether these changes in testicular spermatozoa after freezing and thawing may compromise its use in the ICSI procedure.

Adult↗
PubMed1998

[Massive poisoning by African bee stings].

BACKGROUND: Bee stings can cause severe toxic effects when envenomation is massive. CASE REPORT: While touring in Casamance (Southern Senegal) a white male was severely stung by a swarm of African bees. The massive envenomation caused rhabdomyolysis, hemolysis and acute renal failure. Pathology examination of kidney and bladder specimens showed vasculitis affecting both arteries and veins. The patient was treated with several hemodialysis sessions and renal function returned to normal three months after the incident. DISCUSSION: Bees in Africa, known as "killer bees", are particularly aggressive. They have recently been imported from tropical zones in America where a large number of deaths have been reported. Most cases of massive envenomation have shown acute tubular necrosis or renal involvement with myoglobinuria or hemoglobinuria. The renal pathology observed in our case is not usually described.

Acute Kidney Injury↗
PubMed1998

Deep benign fibrous histiocytoma of the knee: CT and MR features with pathologic correlation.

Magnetic resonance imaging and pathologic findings in a 28-year-old patient with a giant deep benign fibrous histiocytoma in the popliteal fossa of the right knee are described. The MR imaging findings include a well-delineated oval mass with low signal intensity on T1-, and high signal intensity on T2-weighted, images, and marked peripheral contrast enhancement. To the best of our knowledge, this is the first report on the MR findings in this entity.

Adult↗
PubMed1998

Ultrastructure of gametes after intracytoplasmic sperm injection.

The ultrastructure of 18 metaphase-II oocytes after intracytoplasmic sperm injection (ICSI) was analysed from 30 min to 8 h following the microinjection. Three control metaphase-II oocytes were not injected. The 21 oocytes were embedded individually and examined in serial pole-to-pole sections. Seventeen oocytes had been matured in vitro from the germinal vesicle stage and showed ultrastructural alterations due to long-term culture. In microinjected oocytes, membrane-bound vacuoles and oolemma inclusions were found at the injection site. The ICSI oocytes showed evidence of plasma-membrane damage and increased oocyte exchange processes with residual and multivesiculated bodies. Gamete membrane fusion was not observed. Acrosome reaction was observed within the ooplasm 15 min after ICSI. Sperm elements were not incorporated into any oocyte vacuole. Onset of oocyte activation was associated with sperm chromatin decondensation. Cortical granules were released at 60 min and two pronuclei were formed at 6 h after ICSI. The male and female pronucleus formation was asynchronous. The findings suggest specific ICSI-related morphological features of early fertilization.

Cytoplasm↗
PubMed1998

Nasal mucosal sarcoidosis: a case report.

The authors present a case of nasal mucosal sarcoidosis. Its low incidence may be due to unawareness of this sometimes forgotten entity. Crusting and nasal obstruction may be the first symptoms of this multisystemic disease. With the nasal endoscope, today's most helpful tool for examining the nose and its adjacent structures, the otolaryngologist can diagnose this disease at an early stage.

Humans↗